Distribution and expression pattern of claudins 6, 7, and 9 in diffuse- and intestinal-type gastric adenocarcinomas.

Introduction: Intestinal- and diffuse-type gastric adenocarcinomas differ in clinical outcome and genetic profile. Abnormal claudin expression has been well documented in several malignancies. Our aim was to find specific claudin markers for each type.

Methods: Fifty paraffin-embedded tissue blocks of diffuse- and intestinal-type gastric adenocarcinomas and fresh gastric biopsies obtained endoscopically from 20 patients with a presumptive diagnosis of gastric cancer were analyzed. Claudin-specific polyclonal and monoclonal antibodies were used for immunohistochemistry and Western blot analysis in total lysate and subcellular fractions.

Results: Claudin-6 expression was high in both types. Claudin-7 was expressed mainly in the diffuse-type whereas claudin-9 was mainly found in the apical membrane of the gland cells in the intestinal-type. Strong claudin-9 expression was associated with higher mortality rate (66%) in the diffuse type vs the intestinal type (25%) after a 2-year follow-up.

Conclusion: Claudins 6, 7, and 9 expressions are closely related to gastric carcinogenesis, and their detection is a useful prognostic marker in "intestinal-" and "diffuse-type" gastric adenocarcinomas.